# The Impact of Arf1 on Hypoxia Signaling and Oral Cancer

> **NIH NIH R03** · EMORY UNIVERSITY · 2020 · $82,466

## Abstract

PROJECT SUMMARY
 Oral squamous cell carcinoma (OSCC) remains a challenging clinical problem because
of the persisting high rate of local and distant failure. Hypoxia is prevalent in OSCC and often
provides a strong selective pressure for the most aggressive and metastatic tumors, which
emphasize the need for better understanding of molecular mechanisms and regulators
responsible for the acquisition of metastatic potential under hypoxic conditions. We now have
data demonstrating that ADP-ribosylation factor 1 (Arf1), a hypoxia-responsive trafficking
protein, is required and sufficient to hypoxia-induced OSCC invasion and metastasis. The
aberrant overexpression and hyperactivation of Arf1 leads to increased invasion potential upon
hypoxia, raising the possibility to develop novel regimens by targeting Arf1 in order to eventually
increase cure rate in OSCC. Our overarching goal is to improve the survival of patients with
OSCC by revealing the functional consequences of Arf1 dysfunction under hypoxia and
understanding the underlying mechanisms. There are two aims in the proposal to test our
hypothesis. Aim 1 is to dissect the cooperatively transcriptional and epigenetic regulation in
hypoxia-induced Arf1 upregulation. Aim 2 is to Illustrate the molecular mechanism and the
functional consequences of hypoxia-induced Arf1 hyperactivation. These pilot studies will
provide a solid rationale for a more comprehensive investigation into the regulation and role of
Arf1 in hypoxic OSCC for which future R01 mechanism support will be sought. Overall, our
studies will gain mechanistic insight into hypoxia-induced OSCC metastasis by exploring Arf1 as
a novel druggable target for hypoxic tumors, and build a foundation for Arf1-targeted anticancer
therapeutic modality. This project would directly impact the future development of prognostic
variables and treatment strategies for OSCC, especially for those tumors in hypoxic
microenvironment.

## Key facts

- **NIH application ID:** 10422109
- **Project number:** 7R03DE028387-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Yong Teng
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $82,466
- **Award type:** 7
- **Project period:** 2021-06-08 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10422109

## Citation

> US National Institutes of Health, RePORTER application 10422109, The Impact of Arf1 on Hypoxia Signaling and Oral Cancer (7R03DE028387-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10422109. Licensed CC0.

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